Failure of cyclo-oxygenase inhibition to protect against arrhythmias induced by ischaemia and reperfusion: Implications for the role of prostaglandins as endogenous myocardial protective substances

Cherry L. Wainwright, J. Parratt

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Study objective - It has been suggested that the balance between the release from the heart of prostacyclin and thromboxane A2 is a major determinant of the severity of arrhythmias during ischaemia and reperfusion. This has been examined in a dog model.Design - Three different cyclo-oxygenase inhibitors in doses adequate to prevent formation of both prostacyclin and thromboxane - aspirin (7 mg·kg-1), flurbiprofen (3 mg·kg-1), and sodium meclofanate (2 mg·kg-1) with or without nafazatrom or dazmegrel -were given prior to a combined occlusion-reperfusion insult, and the severity of resulting arrhythmias examined.Material - Adult greyhound dogs were used: controls n = 29; aspirin n = 10; flurbiprofen n = 10; sodium meclofenamate ± nafazatrom or dazmegrel n = 22.Measurements and main results - None of the interventions modified the severity of ischaemic arrhythmias induced by coronary artery occlusion and release. The numbers of ventricular extrasy-stoles during the 40 min occlusion period were similar in all groups: controls 653(SEM 109); aspirin 690(187); flurbiprofen 454(132); meclofenamate 833(218). Ventricular fibrillation from the combined occlusion-reperfusion insult was also similar; controls 83%; aspirin 80%; flurbiprofen 80%; meclofenamate 100%. In the doses used all three inhibitors prevented the increase in plasma concentrations of thromboxane A2 [from 104(23) to 166(34) pg·ml-1] and prostacyclin [from 450(80) to 720(110) pg-ml-1] seen in control untreated dogs subjected to coronary artery occlusion. The addition of sodium meclofenamate to either nafazatrom (10 mg·kg-1 orally) or dazmegrel (3 mg·kg-1 intravenously), which when given alone are markedly protective, abolished this protection.Conclusion - The results show the importance of maintaining prostacyclin release in modifying the severity of ischaemic and reperfusion arrhythmias, and again suggest that prostacyclin is an "endogenous antiarrhythmic substance".

Original languageEnglish
Pages (from-to)93-100
Number of pages8
JournalCardiovascular Research
Volume25
Issue number2
DOIs
Publication statusPublished - Jan 1 1991

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Meclofenamic Acid
Flurbiprofen
Epoprostenol
Prostaglandin-Endoperoxide Synthases
Reperfusion
Prostaglandins
Cardiac Arrhythmias
Ischemia
Aspirin
Thromboxane A2
Coronary Occlusion
Dogs
Coronary Vessels
Cyclooxygenase Inhibitors
Thromboxanes
Ventricular Fibrillation
Sodium
Control Groups
nafazatrom
dazmegrel

Keywords

  • Arrhythmias
  • Cyclo-oxygenase inhibitors
  • Myocardial ischaemia
  • Prostanoids
  • Reperfusion

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

@article{33be165591554f10b9d328077370a2ee,
title = "Failure of cyclo-oxygenase inhibition to protect against arrhythmias induced by ischaemia and reperfusion: Implications for the role of prostaglandins as endogenous myocardial protective substances",
abstract = "Study objective - It has been suggested that the balance between the release from the heart of prostacyclin and thromboxane A2 is a major determinant of the severity of arrhythmias during ischaemia and reperfusion. This has been examined in a dog model.Design - Three different cyclo-oxygenase inhibitors in doses adequate to prevent formation of both prostacyclin and thromboxane - aspirin (7 mg·kg-1), flurbiprofen (3 mg·kg-1), and sodium meclofanate (2 mg·kg-1) with or without nafazatrom or dazmegrel -were given prior to a combined occlusion-reperfusion insult, and the severity of resulting arrhythmias examined.Material - Adult greyhound dogs were used: controls n = 29; aspirin n = 10; flurbiprofen n = 10; sodium meclofenamate ± nafazatrom or dazmegrel n = 22.Measurements and main results - None of the interventions modified the severity of ischaemic arrhythmias induced by coronary artery occlusion and release. The numbers of ventricular extrasy-stoles during the 40 min occlusion period were similar in all groups: controls 653(SEM 109); aspirin 690(187); flurbiprofen 454(132); meclofenamate 833(218). Ventricular fibrillation from the combined occlusion-reperfusion insult was also similar; controls 83{\%}; aspirin 80{\%}; flurbiprofen 80{\%}; meclofenamate 100{\%}. In the doses used all three inhibitors prevented the increase in plasma concentrations of thromboxane A2 [from 104(23) to 166(34) pg·ml-1] and prostacyclin [from 450(80) to 720(110) pg-ml-1] seen in control untreated dogs subjected to coronary artery occlusion. The addition of sodium meclofenamate to either nafazatrom (10 mg·kg-1 orally) or dazmegrel (3 mg·kg-1 intravenously), which when given alone are markedly protective, abolished this protection.Conclusion - The results show the importance of maintaining prostacyclin release in modifying the severity of ischaemic and reperfusion arrhythmias, and again suggest that prostacyclin is an {"}endogenous antiarrhythmic substance{"}.",
keywords = "Arrhythmias, Cyclo-oxygenase inhibitors, Myocardial ischaemia, Prostanoids, Reperfusion",
author = "Wainwright, {Cherry L.} and J. Parratt",
year = "1991",
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day = "1",
doi = "10.1093/cvr/25.2.93",
language = "English",
volume = "25",
pages = "93--100",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
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TY - JOUR

T1 - Failure of cyclo-oxygenase inhibition to protect against arrhythmias induced by ischaemia and reperfusion

T2 - Implications for the role of prostaglandins as endogenous myocardial protective substances

AU - Wainwright, Cherry L.

AU - Parratt, J.

PY - 1991/1/1

Y1 - 1991/1/1

N2 - Study objective - It has been suggested that the balance between the release from the heart of prostacyclin and thromboxane A2 is a major determinant of the severity of arrhythmias during ischaemia and reperfusion. This has been examined in a dog model.Design - Three different cyclo-oxygenase inhibitors in doses adequate to prevent formation of both prostacyclin and thromboxane - aspirin (7 mg·kg-1), flurbiprofen (3 mg·kg-1), and sodium meclofanate (2 mg·kg-1) with or without nafazatrom or dazmegrel -were given prior to a combined occlusion-reperfusion insult, and the severity of resulting arrhythmias examined.Material - Adult greyhound dogs were used: controls n = 29; aspirin n = 10; flurbiprofen n = 10; sodium meclofenamate ± nafazatrom or dazmegrel n = 22.Measurements and main results - None of the interventions modified the severity of ischaemic arrhythmias induced by coronary artery occlusion and release. The numbers of ventricular extrasy-stoles during the 40 min occlusion period were similar in all groups: controls 653(SEM 109); aspirin 690(187); flurbiprofen 454(132); meclofenamate 833(218). Ventricular fibrillation from the combined occlusion-reperfusion insult was also similar; controls 83%; aspirin 80%; flurbiprofen 80%; meclofenamate 100%. In the doses used all three inhibitors prevented the increase in plasma concentrations of thromboxane A2 [from 104(23) to 166(34) pg·ml-1] and prostacyclin [from 450(80) to 720(110) pg-ml-1] seen in control untreated dogs subjected to coronary artery occlusion. The addition of sodium meclofenamate to either nafazatrom (10 mg·kg-1 orally) or dazmegrel (3 mg·kg-1 intravenously), which when given alone are markedly protective, abolished this protection.Conclusion - The results show the importance of maintaining prostacyclin release in modifying the severity of ischaemic and reperfusion arrhythmias, and again suggest that prostacyclin is an "endogenous antiarrhythmic substance".

AB - Study objective - It has been suggested that the balance between the release from the heart of prostacyclin and thromboxane A2 is a major determinant of the severity of arrhythmias during ischaemia and reperfusion. This has been examined in a dog model.Design - Three different cyclo-oxygenase inhibitors in doses adequate to prevent formation of both prostacyclin and thromboxane - aspirin (7 mg·kg-1), flurbiprofen (3 mg·kg-1), and sodium meclofanate (2 mg·kg-1) with or without nafazatrom or dazmegrel -were given prior to a combined occlusion-reperfusion insult, and the severity of resulting arrhythmias examined.Material - Adult greyhound dogs were used: controls n = 29; aspirin n = 10; flurbiprofen n = 10; sodium meclofenamate ± nafazatrom or dazmegrel n = 22.Measurements and main results - None of the interventions modified the severity of ischaemic arrhythmias induced by coronary artery occlusion and release. The numbers of ventricular extrasy-stoles during the 40 min occlusion period were similar in all groups: controls 653(SEM 109); aspirin 690(187); flurbiprofen 454(132); meclofenamate 833(218). Ventricular fibrillation from the combined occlusion-reperfusion insult was also similar; controls 83%; aspirin 80%; flurbiprofen 80%; meclofenamate 100%. In the doses used all three inhibitors prevented the increase in plasma concentrations of thromboxane A2 [from 104(23) to 166(34) pg·ml-1] and prostacyclin [from 450(80) to 720(110) pg-ml-1] seen in control untreated dogs subjected to coronary artery occlusion. The addition of sodium meclofenamate to either nafazatrom (10 mg·kg-1 orally) or dazmegrel (3 mg·kg-1 intravenously), which when given alone are markedly protective, abolished this protection.Conclusion - The results show the importance of maintaining prostacyclin release in modifying the severity of ischaemic and reperfusion arrhythmias, and again suggest that prostacyclin is an "endogenous antiarrhythmic substance".

KW - Arrhythmias

KW - Cyclo-oxygenase inhibitors

KW - Myocardial ischaemia

KW - Prostanoids

KW - Reperfusion

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U2 - 10.1093/cvr/25.2.93

DO - 10.1093/cvr/25.2.93

M3 - Review article

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JF - Cardiovascular Research

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